tbuckley/cabot-search huggingface dataset:
Phase III randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) versus DTIC alone as first-line treatment in patients with unresectable stage III or IV melanoma.
Authors: J. D. Wolchok, L. Thomas, I. N. Bondarenko, S. O'Day, J. S. Weber, C. Garbe, S. Francis, R. A. Ibrahim, A. Hoos, C. Robert
Journal: Journal of Clinical Oncology (2011)

LBA5 Background: IPI monotherapy (3mg/kg) improved overall survival (OS) in a phase III study of previously treated, unresectable or metastatic melanoma. Current study in 1st line metastatic melanoma evaluates combination of DTIC (a global standard of care) plus IPI. Methods: In this double-blind phase 3 study, patients (pts) with metastatic melanoma, ECOG PS 0/1, and no prior therapy for advanced disease, were randomized 1:1 to IPI (10 mg/kg) + DTIC (850 mg/m 2 ) or placebo + DTIC (850 mg/m 2 ) at Wks 1, 4, 7, 10 followed by DTIC q3 wks through Wk 22 (induction). Eligible pts received IPI or placebo q12 wks as maintenance. Primary endpoint was OS; 2-sided log-rank test was performed, stratified by baseline M stage and ECOG PS. Results: Of 502 pts, 56% had M1c disease, 40% elevated LDH, and 26% adjuvant therapy. 37% in IPI + DTIC and 65% in DTIC alone arms received 4 induction doses. A significant improvement in OS (HR=0.72; P=0.0009) and higher estimated 1, 2 and 3 yr survival rates were seen with IPI + DTIC (Table). 56% in IPI +DTIC (n=247) and 27% in DTIC alone (n=251) arms had grade 3/4 adverse events (AEs, regardless of attribution), including: elevated ALT (22% vs 1%); diarrhea (4% vs 0%); rash (1% vs 0%). No intestinal perforations or hypophysitis were noted. There were no drug-related deaths in IPI + DTIC and one in DTIC alone arm [gastrointestinal (GI) hemorrhage]. Conclusions: IPI (10mg/kg) + DTIC significantly improved OS in 1st line metastatic melanoma vs DTIC alone; durable survival and objective responses were noted in some pts after follow-up for up to 4yrs. Type of AEs was consistent with prior IPI studies; however, frequencies of some AEs differed with a higher transaminitis and lower diarrhea/colitis/ GI perforation rates than expected. No drug-related deaths were noted in IPI arm. OS benefit of IPI is confirmed in treatment-naive metastatic melanoma. [Table: see text]
Extrachromosomal Probes for Mutagenesis by Carcinogens: Studies on the Mutagenic Activity of O 6 -Methylguanine Built into a Unique Site in a Viral Genome
Authors: John M. Essigmann, Kerry W. Fowler, Calvert L. Green, Edward L. Loechler
Journal: Environmental Health Perspectives (1985)

This work examines the mutagenic activity of 06-methylguanine (O6MeGua), a DNA adduct formed by certain carcinogenic alkylating agents.A tetranucleotide, 5'-HOTpm6GpCpA-3', was synthesized and ligated into a four-base gap in the unique Pst I site of the duplex genome of the E. coli virus, M13mp8.The double- stranded ligation product was converted to single-stranded form and used to transform E. coli to produce progeny phage.The mutation frequency of 06MeGua was defined as the percentage of progeny phage with mutations in their Pst I site, and this value was determined to be 0.4%.To determine the impact of DNA repair on mutagenesis, cellular levels of 06MeGua-DNA methyltransferase (an 06MeGua-repair protein)were depleted by treatment of host cells for virus replication with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) prior to viral DNA uptake.In these host cells, the mutation frequency due to O6MeGua increased markedly with increasing MNNG dose (the highest mutation frequency observed was 20%).DNA sequence analysis of mutant genomes revealed that in both MNNG treated and untreated cells, O6MeGua induced exclusively G to A transitions.
Abstract 2598: Developing small molecule inhibitors that target androgen receptor signaling in castration-resistant prostate cancer
Authors: Balaji Chandrasekaran, Ashish Tyagi, Venkatesh Kolluru, Aakash M. Vadhanam, Becca von Baby, Suresh Gorle, Suman Sirimulla, Srinivasa R. Ramisetti, Arun K. Sharma, Murali K Ankem, Chendil damodaran
Journal: Cancer Research (2019)

Abstract The transcription factor, androgen receptor (AR) is a key driver and plays an important role in prostate cancer. Androgen ablation therapy and brachytherapy remains the standard treatment of advanced prostate cancer, but unfortunately, it is not curative, and eventually the disease returns as lethal castration-resistant prostate cancer (CRPC). Previously we have reported that Urolithin A (Uro A), a natural compound, inhibits AR signaling and suppresses the growth of CRPC. Now, we have developed a series of pro-drug conjugates of Uro A and our initial structure-activity relationship (SAR) studies led to the identification of three small molecules as lead compounds. Hence, we investigated the effects of all three compounds and dissected their molecular mechanism in cell culture and mouse models of CRPC. All the three compounds more effectively inhibited the growth CRPC cell lines than the parent compound Uro A. Based on their IC50 concentration; we identified a novel compound (ASR-600) that demonstrated better efficacy by inhibiting AR signaling in CRPC cell lines than the parental compound Uro A. The model system and molecular dynamics (MD) stimulation studies suggest that ASR600 bind to the ligand-binding domains of AR and blocks the conformation changes, that allows AR to phosphorylate and degrade in the cytosol. Further, our thermal shift assay confirmed ASR 600 binds to AR in presence and absence of Dihydrotestostreone. Our ongoing in vivo studies, may suggest whether oral administration of ASR-600 effectively inhibits the tumor growth raised from CRPC cell lines (C4-2B, 22RV1 and enzalutamide resistance C4-2B) in xenografted mice. These observations provide a rationale for devising novel therapeutic agent based on ASR 600 for the treatment of CRPC Citation Format: Balaji Chandrasekaran, Ashish Tyagi, Venkatesh Kolluru, Aakash M. Vadhanam, Becca von Baby, Suresh Gorle, Suman Sirimulla, Srinivasa R. Ramisetti, Arun K. Sharma, Murali K Ankem, Chendil damodaran. Developing small molecule inhibitors that target androgen receptor signaling in castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2598.
AMERICAN SOCIETY OF HEMATOLOGY Tenth Annual Meeting Toronto, Ontario, Canada, December 3-5, 1967 The Royal York Hotel
Authors: Chester Southam, Robert Lange, Frederick Stohiman, John Schooley, Kurt Reissmann, Robert Allen, Dorothy Moore, James Fisher, Androcens Alexanian, T Kitbridge, Walter Fried, Paul Heller, Inmintor Erythropoietin
Journal: Blood (1967)
Drug treatment of ambulatory patients with hypertension
Journal: JAMA (1973)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The rise and fall (and rise?) of rheumatic fever
Authors: A. L. Bisno
Journal: JAMA (1988)

The dramatic decline in incidence of acute rheumatic fever in the United States during the past half century has been a truly remarkable phenomenon. During the years 1943 to 1945, for example, the incidence of the disease among army personnel stationed in the northeastern United States was 388 per 100 000. As recently as the mid-1960s, rates of approximately 25 to 35 per 100 000 population were recorded among school children in midsized American cities such as Baltimore and Nashville, Tenn. Yet surveys conducted within the past decade in several geographic locales from coast to coast have recorded rheumatic fever incidence rates in the range of 0.5 to 1.88. The experience has been similar in the other highly developed countries of Europe and North America. These facts were commented on in a recent<i>JAMA</i>Landmark Perspective, "The Rise and Fall of Rheumatic Fever,"<sup>1</sup>and were the subject of a
Hemodynamic effects of gallamine and tubocurarine administered during halothane anesthesia
Authors: N. T. Smith
Journal: JAMA (1967)

The hemodynamic effects of gallamine triethiodide or curare administered during halothane anesthesia were investigated in ten volunteer patients before surgery. Cardiac output, heart rate, arterial pressure, and related factors were recorded five to ten times following the administration of either agent. The administration of gallamine increased cardiac output, heart rate, arterial pressure, and left ventricular work; decreased total peripheral resistance and mean transit time; and produced a variable response in stroke volume. Curare decreased arterial pressure and total peripheral resistance, but produced variable changes in other areas. The action of gallamine can be attributed to a cardiovagal block, myocardial stimulation, and a slight sympathetic ganglionic block. The effects of curare arise from a peripheral ganglionic block, myocardial depression, and possible histamine release. The results do not suggest any significant change in the clinical use of either of these neuromuscular blocking agents with halothane.
The Development of Clinical Knowledge
Authors: Paul B. Beeson
Journal: JAMA (1977)

IN THIS symposium I have decided to concentrate on the development of new information about human disease, with special emphasis on the contribution that can be made by clinicians. My own career in academic medicine happens to have coincided with an era of extraordinary activity in biomedical research, in which change has been so rapid and continuous that even those of us who participated find difficulty in appreciating its extent. Here are just a few of the things I have witnessed: effective means for control of heart failure and hypertension, use of steroid hormones, renal dialysis and transplantation, ability to measure and correct fluid and electrolyte disturbances, development of techniques to make the diagnosis of fetal chromosomal abnormality, elimination of erythroblastosis, recognition of the role of lymphoid cells in immune phenomena, discovery of the functions of RNA and DNA (in fact, the whole field of molecular biology), curative treatments for
Pesticide Use in Agriculture
Authors: R. L. Ridgway, J. C. Tinney, J. T. MacGregor, N. J. Starler
Journal: Environmental Health Perspectives (1978)

During the last three decades, the use of modern organic synthetic pesticides has increased about 40-fold. Total U.S. production, for domestic and expert use, in 1976 was about 1.4 million pounds. Crops receiving the most intensive application of various pesticides were cotton for insecticides, corn for herbicides, and fruits and vegetables for fungicides. Examination of use trends of pesticides indicates that the volume in pounds of herbicides used on crops is increasing, whereas the quantities of insecticides and fungicides remain stable. New chemical classes of compounds such as the synthetic pyrethroid insecticides are being introduced, but are not yet significant in terms of their share of the market. The increased usage of pesticides, together with knowledge of some of their adverse effects, has alerted the public to the need for regulation. To assist in the regulatory decision-making process, emphasis is being placed on benefit-cost analyses. Additional and improved biological inputs and methodologies are needed to provide accurate analyses.
Obstruction without dilation. Importance in evaluating jaundice
Authors: C. Beinart
Journal: JAMA (1981)

Transhepatic cholangiography demonstrated no intrahepatic biliary duct dilation in 16 cases of surgical jaundice. The role of ultrasound, computed tomography, and transhepatic cholangiography in differentiating between surgical and medical jaundice is discussed in the light of these 16 cases. Nondilated ducts on ultrasound or computed tomography do not rule out surgical jaundice, and transhepatic cholangiography should be performed for complete evaluation of the biliary tree. (<i>JAMA</i>1981;245:353-356)
Dimethoxyethyl Phthalate: Embryopathy, Teratogenicity, Fetal Metabolism and the Role of Zinc in the Rat
Authors: M. R. Parkhie, M. Webb, M. A. Norcross
Journal: Environmental Health Perspectives (1982)

A single intraperitoneal injection (0.6 ml/kg) of dimethoxyethyl phthalate (DMEP) was given to groups of Wistar strain rats on day 10, 11, 12, 13 or 14 of gestation. Control rats received 0.6 ml/kg of physiological saline intraperitoneally. In phthalate-treated rats, embryopathy was manifested by a high incidence (12-79%) of fetal deaths and fetal resorptions. Fetotoxic effects were expressed by a significant reduction in fetal weights. Hydrocephalus interna, a congenital malformation of the brain, was caused by DMEP. Congenital skeletal deformities (66-96%), with multiple skeletal (14-64%) and appendicular malformations (25-57%), were also induced by DMEP. Control rats exhibited no congenital malformations of the brain and no appendicular or multiple skeletal deformities. DMEP caused a significant decrease in the zinc content of the fetus. Fetoplacental metabolism 1 and 4 hr after intravenous administration of 14C-DMEP suggested rapid transfer of the parent compound to the fetus across the placenta and that DMEP is a teratogenic moiety. The possible role of zinc in phthalate-induced teratogenesis in rats is also discussed.
Commentary
Authors: C Boreham
Journal: British Journal of Sports Medicine (1997)

Energy expenditure in three modes of activity using the Caltrac 239In order to be valid and useful as an activity monitor, instruments or devices must be able to quantify EE accurately and be able to distin- guish between different types and intensities of activity.This study joins others in substantiat- ing that the Caltrac is a reliable instrument.10 However, the Caltrac personal activity monitor was shown to be able to only estimate EE for running, race walking, or stepping in young women.Results from this study suggest that the Caltrac is relatively insensitive in determin- ing individual EE or discriminating energy cost for modes of activity that require different styles of movement patterns.Perhaps when novel movement patterns such as race walking are studied, an accelerometer that is responsive in three dimensions such as the Tritrac 3RD (Hemokinetics, Inc.) may be more appropriate.However, the correlational data support the continued use of the Caltrac in free moving settings when large population data samples are collected especially if an intensity correc- tion factor such as heart rate could be incorporated.Grateful recognition is given to graduate students, Heather Sil- verman, John Noble, and Carol Walker, who assisted in the col- lection of the data.Partial financial support for this
Book Notices
Journal: JAMA (2018)

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Amyloidosis
Authors: Alan S. Cohen
Journal: New England Journal of Medicine (1967)

A UNIQUE disorder causing the liver to be waxy, enlarged and elastic was recognized by a number of pathologists in the early nineteenth century. In 1842 Rokitansky1 observed that the hepatic abnormality was occasionally accompanied by similar changes in the spleen. The widespread nature of this disorder was recognized by Budd,2 Meckel3 and Virchow,4 but it remained for the last to characterize the disease more definitively. Virchow had found that the corpora amylacea of the human brain reacted with iodine and sulfuric acid to give a violet hue, and subsequently observed similar staining in the "lardaceous" liver and spleen.5 6 7 8 He . . .
A Short Practice of Surgery
Journal: JAMA (1941)

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Laboratory Medicine
Journal: JAMA (2001)

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LETTER FROM VIENNA.
Journal: JAMA (1889)

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The Lipid Research Clinics Coronary Primary Prevention Trial Results
Journal: JAMA (1984)

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Lockjaw
Authors: Bill Griffin
Journal: JAMA (2004)

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